Purification and some properties of thiamine-binding protein from rice bran.
A thiamine-binding protein was purified from the extract of rice bran acetone powder by conventional procedures of acid precipitation, a series of column chromatography on DEAE-Sephadex A-50 and DEAE-cellulose, and gel filtration of Sephadex G-200. The purified thiamine-binding protein was nearly homogeneous as judged by disc gel electrophoresis and the molecular weight was estimated to be 94,000 by gel filtration on Sephadex Gn-200 and 50,000 by sodium dodecylsulfate (SDS) gel electrophoresis, suggesting that the protein is composed of two identical subunits. The apparent Kd and Bmax of the binding for [14C]thiamine was 0.44 +/- 0.05 microM and 17.2 +/- 0.7 nmol/mg of protein, respectively. The optimal pH for the binding is between 8.0 and 9.0. From the competition experiment using several thiamine derivatives, high binding specificity of the protein for thiamine was presumed.


[Insularity and epidemic risks in Réunion].
The risks of epidemics in Reunion island depend on determining or favourable factors. The determining factors, links in the epidemic chain, may or may not exist but they can be introduced from the outside. The risk of importing these factors is especially important when the exchanges with the epidemic zones are easy and frequent. Reunion island, at the moment exempt from certain pathologies such as malaria, dengue-fever and urinary Schistosomiasis, is a good example. However, if the presence of these determining factors is necessary, that is not enough in itself. Other factors come into play; in particular physical (leptospirosis) or socio-economic conditions (cysticercosis, intestinal parasitic diseases). The latter play a major role in the hygienic conditions and also in the research and prevention which are easier on an island.


Use of FLOSIC for understanding anion-solvent interactions.
An Achille's heel of lower-rung density-functional approximations is that the highest-occupied-molecular-orbital energy levels of anions, known to be stable or metastable in nature, are often found to be positive in the worst case or above the lowest-unoccupied-molecular-orbital levels on neighboring complexes that are not expected to accept charge. A trianionic example, [Cr(C2O4)3]3-, is of interest for constraining models linking Cr isotope ratios in rock samples to oxygen levels in Earth's atmosphere over geological timescales. Here we describe how crowd sourcing can be used to carry out self-consistent Fermi-Löwdin-Orbital-Self-Interaction corrected calculations (FLOSIC) on this trianion in solution. The calculations give a physically correct description of the electronic structure of the trianion and water. In contrast, uncorrected local density approximation (LDA) calculations result in approximately half of the anion charge being transferred to the water bath due to the effects of self-interaction error. Use of group-theory and the intrinsic sparsity of the theory enables calculations roughly 125 times faster than our initial implementation in the large N limit reached here. By integrating charge density densities and Coulomb potentials over regions of space and analyzing core-level shifts of the Cr and O atoms as a function of position and functional, we unambiguously show that FLOSIC, relative to LDA, reverses incorrect solute-solvent charge transfer in the trianion-water complex. In comparison to other functionals investigated herein, including Hartree-Fock and the local density approximation, the FLOSIC Cr 1s eigenvalues provide the best agreement with experimental core ionization energies.


Dihydropyrrolo[2,3-d]pyrimidines: Selective Toll-Like Receptor 9 Antagonists from Scaffold Morphing Efforts.
Toll-like receptors (TLRs) play important roles in the innate immune system. In fact, recognition of endogenous immune complexes containing self-nucleic acids as pathogen- or damage-associated molecular patterns contributes to certain autoimmune diseases, and inhibition of these recognition signals is expected to have therapeutic value. We identified dihydropyrrolo[2,3-d]pyrimidines as novel selective TLR9 antagonists with high aqueous solubility. A structure-activity relationship study of a known TLR9 antagonist led to the promising compound 18, which showed potent TLR9 antagonistic activity, sufficient aqueous solubility for parenteral formulation, and druggable properties. Compound 18 suppressed the production of the proinflammatory cytokine IL-6 in CpG-induced mouse model. It is therefore believed that compound 18 has great potential in the treatment of TLR9-mediated systemic uncontrollable inflammatory response like sepsis.


Effects of different vaccine combinations against Mycoplasma gallisepticum on the digestive and reproductive organ characteristics of commercial egg-laying hens.
Mycoplasma gallisepticum (MG) is a major and economically significant pathogen of avian species. When administered before lay, F-strain MG (FMG) can reduce egg production during lay, but the ts-11 strain of MG (ts11MG) does not exert this effect. Two trials were conducted to determine the effects of pre-lay vaccinations of ts11MG, MG-Bacterin (MGBac), or their combination, in conjunction with an FMG vaccination overlay after peak production on the digestive and reproductive organ characteristics of Hy-Line W-36 layers housed in biological isolation units (4 units per treatment, 10 birds per unit). The following vaccination treatments were administered at 10 wk of age (woa): 1) Control (no vaccinations); 2) MGBac; 3) ts11MG; and 4) ts11MG and MGBac combination (ts11MG+MGBac). At 45 woa, half of the birds were vaccinated with a laboratory stock of high passage FMG. In both trials, parameters determined in 4 birds per unit at 55 woa included: BW; fatty liver hemorrhagic syndrome incidence; mean number of mature ovarian follicles; ovarian, oviduct, and small intestine weights; and the weights and lengths of the various portions of the oviduct and small intestine. Treatment effects were observed for the weights of the entire small intestine and the duodenum, jejunum, and ileum, as percentages of BW; and for vagina weight as a percentage of total oviduct weight. In general, the weights of the small intestine and its 3 components were increased in response to the FMG vaccine that was administered at 45 woa. An FMG vaccination at 45 woa may increase relative intestine weight in layers; however, use of a prelay MGBac vaccine alone or in combination with ts11MG, with or without an FMG overlay, does not affect the gross characteristics of their digestive and reproductive organs, and may be used without having an adverse effect on their performance, as was observed in a previous companion study.


Passiflora manicata (Juss.) aqueous leaf extract protects against reactive oxygen species and protein glycation in vitro and ex vivo models.
The leaf extracts of many species of genus Passiflora have been extensively investigated for their biological activities on several rat tissues, but mainly in the central nervous system and liver. They posses anxiolytic-like, sedative effects and antioxidant properties. Evidences suggest a key role of C-glycosylflavonoids in the biological activities of Passiflora extracts. Some species (such as P. manicata) of the genus are still poorly investigated for their chemical and biological activity. In this work, we aim to investigate both antioxidant and antiglycation properties of aqueous extract of P. manicata leaves (PMLE) in vitro and ex vivo models. Crude extract showed the C-glycosylflavonoid isovitexin as the major compound. Isoorientin and vitexin were also identified. In TRAP/TAR assay, PMLE showed a significant antioxidant activity. PMLE at concentrations of 10 and 100 μg mL⁻¹ significantly decreasing LDH leakage in rat liver slices. Antioxidant effect also was observed by decreased in oxidative damage markers in slices hence hydrogen peroxide was added as oxidative stress inductor. PMLE inhibited protein glycation at all concentrations tested. In summary, P. manicata aqueous leaf extract possess protective properties against reactive oxygen species and also protein glycation, and could be considered a new source of natural antioxidants.


Developing emotional insulation.
An important goal of therapy is to help patients develop ego boundaries that are flexible and adaptive. This paper proposes use of the term "insulation barrier" to describe the defensive structure that allows a person to withstand toxic stimuli and also enables nutrient experiences to flow through. There is no better arena in which to develop a serviceable insulation barrier than group therapy. In this setting the insulation deficiencies of both rigid overinsulated patients and oversensitive underinsulated ones are easily diagnosed. The author explicates specific techniques that the therapist may employ to help patients become aware of their limitations and practice ways of reacting to stimuli that make them more receptive to new learning.


Beam smoothing by introducing spatial dispersion for high-peak-power laser pulse compression.
Post-compression can effectively further improve the peak power of laser pulses by shortening the pulse duration. Which has been investigated in various ranges of energy and central wavelength. However, the spatial intensity profile of high-peak-power laser pulses is generally inhomogeneous due to pump lasers, imperfect optical components, and dust in the optical layout. In post-compression, the B-integral is proportional to intensity, and wavefront distortions are induced in the spectral broadening stage, leading to a decrease in focusing intensity. Moreover, the beam intensity may be strongly modulated and beam inhomogeneity will be intensified in this process, causing damage to optical components and limiting the achievement of high peak power enhancement. In this study, to address these challenges, the laser pulse is first smoothed by introducing spatial dispersion using prism pairs or asymmetric four-grating compressors, and then the smoothed pulse is used for post-compression. The simulation results indicate that this method can effectively remove hot spots from laser pulses and maintain high peak power enhancement in post-compression.


Cortisol, Amyloid-β, and Reserve Predicts Alzheimer's Disease Progression for Cognitively Normal Older Adults.
Elevated cortisol as a measure of hypothalamic-pituitary-adrenal-axis hyperactivity has emerged as a predictor of clinical progression of Alzheimer's disease (AD), in conjunction with amyloid-β (Aβ) abnormalities. Yet factors exist which have the propensity to delay AD symptomatic expression in the face of an AD-type biomarker-based pathological profile. This study sought to determine whether abnormal cerebrospinal fluid (CSF) Aβ and elevated cortisol levels are associated with clinical transition to mild cognitive impairment (MCI) and AD in cognitively normal (CN) individuals, and if this association is modified by reserve proxies. Data from 91 CN individuals participating in the Alzheimer's Disease Neuroimaging Initiative (ADNI) with available morning CSF cortisol and Aβ42 were evaluated. Reserve was modelled as a latent composite score of standardized intracranial volume and lifetime experience proxies. Cox regressions were used to test associations between baseline CSF cortisol/Aβ42, reserve score and AD progression; adjusting for age, sex, apolipoprotein E genotype, and depressive symptoms. Individuals with elevated cortisol + abnormal Aβ42 levels at baseline showed highest risk of clinical progression. After a median of 84 months follow-up, significant cortisol/Aβ/ reserve interaction for clinical progression was noted (adjusted HR = 0.15, p < 0.001), suggesting a moderating effect of reserve on the association between cortisol/Aβ+ and clinical progression. Our findings indicate that cortisol hypersecretion accelerates clinical progression in CN individuals presenting with pathological Aβ42. High reserve reduces the associated AD progression risk in these high-risk individuals.


An Empirical Orthogonal Function-Based Algorithm for Estimating Terrestrial Latent Heat Flux from Eddy Covariance, Meteorological and Satellite Observations.
Accurate estimation of latent heat flux (LE) based on remote sensing data is critical in characterizing terrestrial ecosystems and modeling land surface processes. Many LE products were released during the past few decades, but their quality might not meet the requirements in terms of data consistency and estimation accuracy. Merging multiple algorithms could be an effective way to improve the quality of existing LE products. In this paper, we present a data integration method based on modified empirical orthogonal function (EOF) analysis to integrate the Moderate Resolution Imaging Spectroradiometer (MODIS) LE product (MOD16) and the Priestley-Taylor LE algorithm of Jet Propulsion Laboratory (PT-JPL) estimate. Twenty-two eddy covariance (EC) sites with LE observation were chosen to evaluate our algorithm, showing that the proposed EOF fusion method was capable of integrating the two satellite data sets with improved consistency and reduced uncertainties. Further efforts were needed to evaluate and improve the proposed algorithm at larger spatial scales and time periods, and over different land cover types.


[Accelerated plastic surgery using inguinal flap on temporary feeding pedicle].
The method of accelerated plasty with an inguinal flap was used for treatment of 13 patients with electric burns and frostbites of the IV degree. The 2nd step of the non-free skin plasty was performed 5 days (120 hours) after the first operation which was possible following a special training--a periodical, with increasing duration of the compression of the flap feeding pedicle which was started next day after the first step of the plasty.


Incidence of type 1 diabetes mellitus diagnosed before age 20 years in Canterbury, New Zealand over the last 30 years.
This study examined the epidemiological characteristics of type 1 diabetes mellitus (DM) presenting in Canterbury, New Zealand, between 1970 and 1999. All patients with type 1 DM aged 0-19 years at diagnosis within the Canterbury geographical region were either admitted to the regional hospital or seen acutely as outpatients in clinics at the same institution. Primary ascertainment of incident cases, through notification by the attending physician or paediatrician, began prospectively in 1982. Incident cases between 1970 and 1982 were ascertained retrospectively from clinic and hospital records. For the years 1970-99, there were 474 incident cases (256 males, 218 females). Incidence rates determined from 5-yearly census population denominators ranged from 2.40 to 26.59 patients/100,000 person years. The mean for 5-year periods, starting from 1970, increased from 6.79 to 22.79 patients/100,000 person years, i.e. a 3.4-fold increase over 30 years. The increase in incidence based on linear regression of these data is 0.59 patients/100,000 per year, or an annual increase of 5% derived from regression of the natural logarithms of the incidence data. These observations are consistent with the increasing attack rates for type 1 DM reported worldwide.


A peculiar configuration of agranular reticulum (canaliculate lamellar body) in the rat pinealocyte.
A cytoplasmic structure exhibiting a peculiar configuration of agranular reticulum has been found in the rat pinealocyte, and has been designated a canaliculate lamellar body. It consists of a number of fenestrated, flat cisternae which are closely spaced. They bear some distant resemblance to the annulate lamellae previously reported in a variety of cell types. Profiles of stacks of lamellae in a plane of section always display two distinct aspects, the surface and the cross-sectional views of flat cisternae. A surface view shows the hexagonal arrangement of pores or fenestrations. The pores in successive lamellae are aligned precisely, one behind the other, so that clear, cylindrical channels are seen running perpendicular to the lamellae as indicated by transverse sections of the lamellar stacks. Large canaliculate lamellar bodies are composed of many extended series of lamellar stacks which pursue a tortuous course and cross one another. Occasionally the canaliculate lamellar body is located deep in a nuclear invagination, which reminds one of the so-called nuclear pellets (Kernkugeln) reported by light microscopy. The functional significance of the body is unknown.


Non-invasive quantification of myocardial blood flow and flow reserve using dynamic positron emission tomography.
Positron Emission Tomography (PET) permits the non-invasive quantification of myocardial blood flow and flow reserve. This capability requires an understanding of the determinants of resting and hyperemic blood flow in order to interpret correctly quantitative findings with PET. Equally important is the knowledge of how such measurements are obtained and of their advantages and limitations. The aim of the current overview was therefore a) to review the concept of the myocardial flow reserve and b) to discuss recent animal experimental and clinical studies which have employed quantitative PET for measuring myocardial blood flow and flow reserve.


Phytoextraction of Cadmium and Zinc By Sedum plumbizincicola Using Different Nitrogen Fertilizers, a Nitrification Inhibitor and a Urease Inhibitor.
Cadmium (Cd) and zinc (Zn) phytoavailability and their phytoextraction by Sedum plumbizincicola using different nitrogen fertilizers, nitrification inhibitor (dicyandiamide, DCD) and urease inhibitor (N-(n-Butyl) thiophosphoric triamide, NBPT) were investigated in pot experiments where the soil was contaminated with 0.99 mg kg(-1) of Cd and 241 mg kg(-1) Zn. The soil solution pH varied between 7.30 and 8.25 during plant growth which was little affected by the type of N fertilizer. The (NH4)2SO4+DCD treatment produced higher NH4+-N concentrations in soil solution than the (NH4)2SO4 and NaNO3 treatment which indicated that DCD addition inhibited the nitrification process. Shoot Cd and Zn concentrations across all treatments showed ranges of 52.9-88.3 and 2691-4276 mg kg(-1), respectively. The (NH4)2SO4+DCD treatment produced slightly higher but not significant Cd and Zn concentrations in the xylem sap than the NaNO3 treatment. Plant shoots grown with NaNO3 had higher Cd concentrations than (NH4)2SO4+DCD treatment at 24.0 and 15.4 mg kg(-1), respectively. N fertilizer application had no significant effect on shoot dry biomass. Total Cd uptake in the urea+DCD treatment was higher than in the control, urea+NBPT, urea+NBPT+DCD, or urea treatments, by about 17.5, 23.3, 10.7, and 25.1%, respectively.


¿Where do migratory fish spawn in a neotropical Andean basin regulated by dams?
Spawning sites play a key role in the reproduction of fish allowing populations to endure over time. The Nechí River is an important spawning area for potamodromous fish species where one of the threats is dam construction. In order to determine the importance of the Nechí River as a spawning site in the Magdalena River basin, sampling was conducted during the low-water-to-high-water season transition period between 2018 and 2019 at seven sampling sites. The average density of ichthyoplankton was 42.4 ind.10m-3 (SD = 7.1). Of the individuals in the post-larval stage, seven migratory species were identified, and two additional taxa were identified to genus; Prochilodus magdalenae, Megaleporinus muyscorum, and Pseudoplatystoma magdaleniatum presented the greatest density. At the temporal level, the greatest density of larvae of potamodromous species was observed in the first high-water season of 2019 with a total of 5.7 ind.10m-3(SD = 1.044), of which the most representative at the seasonal level were the Cauca River, Magdalena River, and Nechí River before it flows into the Cauca River. There were significant differences in the frequency of embryos and vitelline larvae of the potamodromous species in the interaction of the sampling sites and high-water seasons, as well as with the density of post-larvae. The average drift distance of the spawning areas is roughly 52.1 km. A positive association was found between the volume of turbined water and the presence of ichthyoplankton in the Porce River site, after discharge from the Porce III Hydroelectric Plant. The Nechí River is an important spawning site and there seems to be an association between the increase in ichthyoplankton densities and the distance to the dam (Porce III) as long as there are floodplains along the course of the river.


Comparative proteomic analysis using samples obtained with laser microdissection and saturation dye labelling.
Comparative proteomic methods are rapidly being applied to many different biological systems including complex tissues. One pitfall of these methods is that in some cases, such as oncology and neuroscience, tissue complexity requires isolation of specific cell types and sample is limited. Laser microdissection (LMD) is commonly used for obtaining such samples for proteomic studies. We have combined LMD with sensitive thiol-reactive saturation dye labelling of protein samples and 2-D DIGE to identify protein changes in a test system, the isolated CA1 pyramidal neurone layer of a transgenic (Tg) rat carrying a human amyloid precursor protein transgene. Saturation dye labelling proved to be extremely sensitive with a spot map of over 5,000 proteins being readily produced from 5 mug total protein, with over 100 proteins being significantly altered at p < 0.0005. Of the proteins identified, all showed coherent changes associated with transgene expression. It was, however, difficult to identify significantly different proteins using PMF and MALDI-TOF on gels containing less than 500 mug total protein. The use of saturation dye labelling of limiting samples will therefore require the use of highly sensitive MS techniques to identify the significantly altered proteins isolated using methods such as LMD.


Nitrogen fertilization rates mediate rhizosphere soil carbon emissions of continuous peanut monoculture by altering cellulose-specific microbess.
Crops influence both soil microbial communities and soil organic carbon (SOC) cycling through rhizosphere processes, yet their responses to nitrogen (N) fertilization have not been well investigated under continuous monoculture. In this study, rhizosphere soil microbial communities from a 5-year continuous mono-cropped peanut land were examined using Illumina HighSeq sequencing, with an N fertilization gradient that included 0 (N0), 60 (N60), 120 (N120) and 180 (N180) kg hm-2. Soil respiration rate (R s) and its temperature sensitivity (Q 10) were determined, with soil carbon-acquiring enzyme activities assayed. The obtained results showed that with N fertilization, soil mineral N (Nmin) was highly increased and the soil C/N ratio was decreased; yields were unchanged, but root biomass was stimulated only at N120. The activities of β-1,4-glucosidase and polyphenol oxidase were reduced across application rates, but that of β-1,4-cellobiohydrolase was increased only at N120. Bacterial alpha diversity was unchanged, but fungal richness and diversity were increased at N60 and N120. For bacterial groups, the relative abundance of Acidobacteria was reduced, while those of Alphaproteobacteria and Gammaproteobacteria were increased at N60 and N120. For fungal members, the pathogenic Sordariomycetes was inhibited, but the saprotrophic Agaricomycetes was promoted, regardless of N fertilization rates. RDA identified different factors driving the variations in bacterial (root biomass) and fungal (Nmin) community composition. N fertilization increased R s slightly at N60 and significantly at N120, mainly through the promotion of cellulose-related microbes, and decreased R s slightly at N180, likely due to carbon limitation. N fertilization reduced microbial biomass carbon (MBC) at N60, N120 and N180, decreased SOC at N120 and N180, and suppressed dissolved organic carbon (DOC) at N180. In addition, the unchanged Q 10 may be a joint result of several mechanisms that counteracted each other. These results are of critical importance for assessing the sustainability of continuously monocultured ecosystems, especially when confronting global climate change.


One case of confluent and reticulate papillomatosis (Gougerot-Carteaud).
A 16-year-old girl with dark-brown coalescing papules symmetrically localized to the cheeks, is reported. The diagnosis may be consistent with the criteria for confluent and reticulate papillomatosis (Gougerot-Carteaud). The association between this disease and Pityrosporum orbiculare is discussed.


Post-treatment plasma transforming growth factor beta 1 (TGF-beta1) level predicts for late morbidity in patients with advanced head and neck cancer.
Between 2001 and 2002, 29 patients with advanced inoperable squamous head and neck cancer treated with radiotherapy with or without simultaneous chemotherapy were evaluated for their plasma TGF-beta1 levels prior to the treatment, in the middle of the radiotherapy course and at the end of the treatment. Patients were assessed for treatment response and late morbidity. Predictive value of TGF-beta1 level on either of the assessed parameters was tested. From 29 eligible patients (pts), 18 achieved complete response, 8 partial response and three pts progressed primarily. After a median follow-up of 16 months we recorded 16 cases of grade >1 late morbidity. We found that post-treatment elevated plasma TGF-beta1 level predicts late morbidity grade >1 (p=0.05) rather than pre-treatment level (p=0.062). Neither pre-treatment nor post-treatment plasma TGF-beta1 level has a predictive value to the treatment response (CR vs. no CR, p=0.125 and 0.252, respectively). The post-treatment plasma TGF-beta 1 level can predict late morbidity grade >1 in advanced head and neck cancer treated with radio(chemo)therapy. This could make a basis for dose escalation in selected patients.


[Function of Tra2beta1 proteins in the splicing of neural-specific genes].
The in vitro studies have shown that Tra2beta1 proteins are important regulators in the alternative pre-mRNA splicing in mammalians. To date, the knowledge regarding the in vivo function of Tra2beta1 proteins, especially the function in regulating the splicing of neural-specific genes and the cell-type specificity of the functions is very limited. In the present study, the cell-type specific splicing of two neural-specific genes (GluR-B and SMN2), and the function of Tra2beta1 proteins in regulation of the splicing were studied in two types of cells (COS-1 and PFSK-1) using in vivo splicing models. The results showed that the splicing of GluR-B and SMN2 minigenes is cell-type specific, while Tra2beta1 proteins regulate the splicing of the minigenes in both cell lines in a similar pattern. It indicates that the Tra2beta1-regulated splicing of GluR-B and SMN2 minigenes regulated by Tra2beta1 is not cell-type specific.


Rate constants for hydrogen abstraction from alkoxides by a perfluoroalkyl radical. An oxyanion accelerated process.
A combination of laser flash photolysis and competitive kinetic methods has been used to measure the absolute bimolecular rate constants for hydrogen atom abstraction in water from a series of fluorinated alkoxides and aldehyde hydrates by the perfluoroalkyl radical, *CF2CF2OCF2CF2SO3- Na+. The bimolecular rate constants observed for the beta-fluorinated alkoxides were in the 10(5) M(-1) s(-1) range, such rates representing enhancements (relative to the respective alcohols) of between 100 and almost 1000-fold, depending on the reactivity of the alkoxide. Likewise, the monobasic sodium salts of chloral and fluoral hydrate exhibit similar rate enhancements, relative to their respective hydrates.


Medical Treatment for Postthrombotic Syndrome.
Deep vein thrombosis (DVT) is a prevalent disease. About 20 to 30% of patients with DVT will develop postthrombotic syndrome (PTS) within months after the initial diagnosis of DVT. There is no gold standard for diagnosis of PTS, but clinical signs include pitting edema, hyperpigmentation, phlebectatic crown, venous eczema, and varicose veins. Several scoring systems have been developed for diagnostic evaluation. Conservative treatment includes compression therapy, medications, lifestyle modification, and exercise. Compression therapy, the mainstay and most proven noninvasive therapy for patients with PTS, can be prescribed as compression stockings, bandaging, adjustable compression wrap devices, and intermittent pneumatic compression. Medications may be used to both prevent and treat PTS and include anticoagulation, anti-inflammatories, vasoactive drugs, antibiotics, and diuretics. Exercise, weight loss, smoking cessation, and leg elevation are also recommended. Areas of further research include the duration, compliance, and strength of compression stockings in the prevention of PTS after DVT; the use of intermittent compression devices; the optimal medical anticoagulant regimen after endovascular therapy; and the role of newer anticoagulants as anti-inflammatory agents.


Evaluation of the culling variate used by breeders in actual selection.
The theoretical basis and computational procedures for estimating the culling variate utilized by breeders in actual selection are presented. The essential part of this procedure is to derive the unknown culling variate in terms of a linear combination of traits based on realized indirect selection differentials of those traits and phenotypic variances and covariances among traits in the population. Special emphasis is placed on the distribution of the variables involved. The accuracy of the culling variates is estimated by use of the biserial correlation with some modifications. Numerical illustrations are given for different types of selection.


Polyphasic taxonomic analysis of Sinimarinibacterium arenosum sp. nov., a halophilic bacterium isolated from marine sediment.
A Gram stain-negative, aerobic, motile, rod-shaped bacterial strain, designated CAU 1509T, was isolated from marine sediment, and its taxonomic position was determined using a polyphasic approach. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain CAU 1509T formed a distinct lineage within the genus Sinimarinibacterium with the highest 16S rRNA gene sequence similarity to Sinimarinibacterium flocculans NH6-24T (97.0%). Similar to another member of Sinimarinibacterium, ubiquinone-8 (Q-8) was the predominant quinone, whereas C16:0, summed feature 3 (C16:1ω7c/ω6c) and summed feature 8 (C18:1ω7c/ω6c) were the major cellular fatty acids. The major polar lipids were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, an unidentified phospholipid, four unidentified glycolipids and three unidentified aminolipids. Strain CAU 1509T has a genome of 4.54 Mb, including 4251 coding sequences, 6 rRNAs and 50 tRNAs, with a genomic DNA G+C content of 63.2 mol%. Based on its phenotypic, chemotaxonomic and phylogenetic properties, strain CAU 1509T should be classified as a novel species of the genus Sinimarinibacterium, for which the name Sinimarinibacterium arenosum sp. nov. is proposed. The type strain is CAU 1509T (= KCTC 72000T = NBRC 113698T).


Wharton's jelly mesenchymal stem cells: a concise review of their secretome and prospective clinical applications.
Accumulating evidence indicates that most primary Wharton's jelly mesenchymal stem cells (WJ-MSCs) therapeutic potential is due to their paracrine activity, i.e., their ability to modulate their microenvironment by releasing bioactive molecules and factors collectively known as secretome. These bioactive molecules and factors can either be released directly into the surrounding microenvironment or can be embedded within the membrane-bound extracellular bioactive nano-sized (usually 30-150 nm) messenger particles or vesicles of endosomal origin with specific route of biogenesis, known as exosomes or carried by relatively larger particles (100 nm-1 μm) formed by outward blebbing of plasma membrane called microvesicles (MVs); exosomes and MVs are collectively known as extracellular vesicles (EVs). The bioactive molecules and factors found in secretome are of various types, including cytokines, chemokines, cytoskeletal proteins, integrins, growth factors, angiogenic mediators, hormones, metabolites, and regulatory nucleic acid molecules. As expected, the secretome performs different biological functions, such as immunomodulation, tissue replenishment, cellular homeostasis, besides possessing anti-inflammatory and anti-fibrotic effects. This review highlights the current advances in research on the WJ-MSCs' secretome and its prospective clinical applications.


Midtrimester screening for microalbuminuria in healthy pregnant women.
To ascertain the effectiveness and feasibility of testing for microalbuminuria and the albumin/creatinine ratio as an early indication of hypertensive disorders of pregnancy, we measured albumin and creatinine excretion in 95 healthy pregnant women between 16 and 20 weeks of pregnancy. Nine women developed hypertensive complications; one of them became pre-eclamptic. There were no statistically significant differences in urine albumin and creatinine concentrations nor in the albumin/creatinine ratio between those women who developed pregnancy-induced hypertension and those who did not. Microalbuminuria testing had a specificity of 0.95 (95% CI: 0.88 - 0.99) and a sensitivity of 0.11 (95% CI: 0.03 - 0.48). The albumin/creatinine ratio had a specificity of 0.98 (95% CI: 0.92 - 1.0) and a sensitivity of 0.22 (95% CI: 0.03 - 0.6). The albumin/creatinine ratio was significantly lower in women who delivered prematurely. We conclude that mid-trimester testing for microalbuminuria and the measurement of the urinary albumin/creatinine ratio are not effective tools for the early recognition of pregnancy-induced hypertension in healthy pregnant women.


Assessing the Need for Higher Levels of Care Among Problem Gambling Outpatients.
Most treatment for gambling disorder is provided on an outpatient basis. Only a small number of jurisdictions in North America provide higher levels of gambling treatment, such as residential or intensive outpatient (IOP) care, despite the potential need for these services. Further, there appear to be few guidelines for determining appropriate level of gambling treatment. The aim of the present study was to assess the appropriateness of higher levels of problem gambling care among clients receiving outpatient treatment. Problem gamblers and their therapists independently completed questionnaires that assessed the need and desire for residential and IOP treatment. About 42% of problem gambling outpatients noted that they would be "probably" or "definitely" willing to attend residential treatment, and about half indicated they would be equally likely to attend IOP. Therapists recommended about a third of their clients as appropriate for higher levels of care. For both client and therapist assessments, there was a significant association between desire or recommendation for level of treatment and severity of gambling and co-occurring problems. Further, therapist recommendations for level of care were significantly associated with client willingness to attend higher levels of treatment. Our data reveal the potential need for higher levels of care for problem gambling, as evaluated by clients and their therapists. Policy implications for the funding of residential and IOP treatment are discussed.


Randomized clinical trial of perioperative selective decontamination of the digestive tract versus placebo in elective gastrointestinal surgery.
This randomized clinical trial analysed the effect of perioperative selective decontamination of the digestive tract (SDD) in elective gastrointestinal surgery on postoperative infectious complications and leakage. All patients undergoing elective gastrointestinal surgery during a 5-year period were evaluated for inclusion. Randomized patients received either SDD (polymyxin B sulphate, tobramycin and amphotericin) or placebo in addition to standard antibiotic prophylaxis. The primary endpoint was postoperative infectious complications and anastomotic leakage during the hospital stay or 30 days after surgery. A total of 289 patients were randomized to either SDD (143) or placebo (146). Most patients (190, 65·7 per cent) underwent colonic surgery. There were 28 patients (19·6 per cent) with infectious complications in the SDD group compared with 45 (30·8 per cent) in the placebo group (P = 0·028). The incidence of anastomotic leakage in the SDD group was 6·3 per cent versus 15·1 per cent in the placebo group (P = 0·016). Hospital stay and mortality did not differ between groups. Perioperative SDD in elective gastrointestinal surgery combined with standard intravenous antibiotics reduced the rate of postoperative infectious complications and anastomotic leakage compared with standard intravenous antibiotics alone. Perioperative SD.D should be considered for patients undergoing gastrointestinal surgery. P02.1187L (Dutch Central Committee on Research Involving Human Subjects).


Efficient exploration of transition-metal decorated MXene for carbon monoxide sensing using integrated active learning and density functional theory.
The urgent demand for chemical safety necessitates the real-time detection of carbon monoxide (CO), a highly toxic gas. MXene, a 2D material, has shown potential for gas sensing applications (e.g., NH3, NO, SO2, CO2) due to its high surface accessibility, electrical conductivity, stability, and flexibility in surface functionalization. However, the pristine MXene generally exhibits poor interaction with CO; still, transition metal decoration can strengthen the interaction between CO and MXene. This study presents a high-throughput screening of 450 combinations of transition-metal (TM) decorated MXene (TM@MXene) for CO sensing applications using an integrated active learning (AL) and density functional theory (DFT) screening pipeline. Our AL pipeline, adopting a crystal graph convolutional neural network (CGCNN) as a surrogate model, successfully accelerates the screening of CO sensor candidates with minimal computational resources. This study identifies Sc@Zr3C2O2 and Y@Zr3C2O2 as the optimal TM@MXene candidates with promising CO sensing performance regarding the screening criteria of recovery time, surface stability, charge transfer, and sensitivity to CO. The proposed AL framework can be extended for property finetuning in the combinatorial chemical space.


Systematic search for mutations in the 14-3-3 eta chain gene on chromosome 22 in schizophrenics.
The brain-rich 14-3-3 protein regulates synthesis and excretion of bioamine by activating tyrosine and tryptophan hydroxylases, and by exocytosis of catecholamines and serotonin. In humans, at least eight subunits of the 14-3-3 protein family have been isolated. The 14-3-3 eta chain gene is located at 22q12.1 to q13.1, one of the chromosome regions identified as possibly linked to schizophrenia. We systematically searched for nucleotide variants in the coding region, 5' and 3' untranslated region, and in the exon-intron boundaries of the genomic 14-3-3 eta gene in 24 schizophrenics and 24 controls. Two polymorphic sites were found: one in the 5' untranslated region and one in the 3' untranslated region. However, no variants predicting amino-acid alterations were observed. Similar allelic and genotypic distributions for both polymorphisms were found in 308 schizophrenics and 135 controls.


Design and Characterization of a Multifunctional pH-Triggered Peptide C8 for Selective Anticancer Activity.
Most drug delivery systems have been developed for efficient delivery to tumor sites via targeting and on-demand strategies, but the carriers rarely execute synergistic therapeutic actions. In this work, C8, a cationic, pH-triggered anticancer peptide, is developed by incorporating histidine-mediated pH-sensitivity, amphipathic helix, and amino acid pairing self-assembly design. We designed C8 to function as a pH-responsive nanostructure whose cytotoxicity can be switched on and off by its self-assembly: Noncytotoxic β-sheet fibers at high pH with neutral histidines, and positively charged monomers with membrane lytic activity at low pH. The selective activity of C8, tested for three different cancer cell lines and two noncancerous cell lines, is shown. Based on liposome leakage assays and multiscale computer simulations, its physical mechanisms of pore-forming action and selectivity are proposed, which originate from differences in the lipid composition of the cellular membrane and changes in hydrogen bonding. C8 is then investigated for its potential as a drug carrier. C8 forms a nanocomplex with ellipticine, a nonselective model anticancer drug. It selectively targets cancer cells in a pH-responsive manner, demonstrating enhanced efficacy and selectivity. This study provides a novel powerful strategy for the design and development of multifunctional self-assembling peptides for therapeutic and drug delivery applications.


Cucurbitacins: elucidation of their interactions with the cytoskeleton.
Cucurbitacins, a class of toxic tetracyclic triterpenoids in Cucurbitaceae, modulate many molecular targets. Here we investigated the interactions of cucurbitacin B, E and I with cytoskeletal proteins such as microtubule and actin filaments. The effects of cucurbitacin B, E and I on microtubules and actin filaments were studied in living cells (Hela and U2OS) and in vitro using GFP markers, immunofluorescence staining and in vitro tubulin polymerization assay. Cucurbitacin B, E and I apparently affected microtubule structures in living cells and cucurbitacin E inhibited tubulin polymerization in vitro with IC50 value of 566.91 ± 113.5 µM. Cucurbitacin E did not affect the nucleation but inhibited the growth phase and steady state during microtubule assembly in vitro. In addition, cucurbitacin B, E and I all altered mitotic spindles and induced the cell cycle arrest at G2/M phase. Moreover, they all showed potent effects on actin cytoskeleton by affecting actin filaments through the depolymerization and aggregation. The interactions of cucubitacin B, E and I with microtubules and actin filaments present new insights into their modes of action.


Reaction sequence of iron sulfide minerals in bacteria and their use as biomarkers.
Some bacteria form intracellular nanometer-scale crystals of greigite (Fe3S4) that cause the bacteria to be oriented in magnetic fields. Transmission electron microscope observations showed that ferrimagnetic greigite in these bacteria forms from nonmagnetic mackinawite (tetragonal FeS) and possibly from cubic FeS. These precursors apparently transform into greigite by rearrangement of iron atoms over a period of days to weeks. Neither pyrrhotite nor pyrite was found. These results have implications for the interpretation of the presence of pyrrhotite and greigite in the martian meteorite ALH84001.


[Revascularization of left anterior descending artery area using a skeletonized left internal mammary artery: a comparison between sequential and separate grafting].
Objective: To evaluate in-hospital and mid-term outcomes of sequential versus separate grafting of in situ skeletonized left internal mammary artery (LIMA) to the left coronary system in a single-center, propensity-matched study. Methods: After propensity score matching, 120 pairs of patients undergoing first, scheduled, isolated coronary artery bypass grafting (CABG) with in situ skeletonized LIMA grafting to the left anterior descending artery (LAD) territory were entered into a sequential group (sequential grafting of LIMA to the diagonal artery and then to the LAD) or a control group (separate grafting of LIMA to the LAD). The in-hospital and follow-up clinical outcomes and follow-up LIMA graft patency were compared. Results: The two propensity score-matched groups had similar in-hospital and follow-up clinical outcomes. The number of bypass conduits ranged from 3 to 6 (with a mean of 3.5), and 91.3%(219/240)of the included patients received off-pump CABG surgery. No significant differences were found between the two propensity score-matched groups in the in-hospital outcomes, including in-hospital death and the incidence of complications associated with CABG (prolonged ventilation, peroperative stroke, re-operation before discharge, and deep sternal wound infection). During follow-up, 9 patients (4 patients from the sequential group and 5 patients from the control group) died, and the all-cause mortality rate was 3.9%. No significant difference was found in the all-cause mortality rate between the 2 groups[3.4% (4/116) vs 4.3% (5/115), P=0.748]. During follow-up period, 99.1% (115/116) patency for the diagonal site and 98.3% (114/116) for the LAD site were determined by coronary computed tomographic angiography after sequential LIMA grafting, both of which were similar with graft patency of separate grafting of in situ skeletonized LIMA to the LAD. Conclusions: Revascularization of the left coronary system using a skeletonized LIMA resulted in excellent in-hospital and mid-term clinical outcomes and graft patency using sequential grafting.


Treatment of synthetic kraft evaporator condensate using thermophilic and mesophilic membrane aerated biofilm reactors.
A comparative study on the treatment of synthetic kraft evaporator condensate was conducted using thermophilic (55 degrees C) and mesophilic (30 degrees C) membrane aerated biofilm reactors (MABRs) and sequencing batch reactors (SBRs) for 8 months. Under tested conditions, a chemical oxygen demand (COD) removal efficiency of 80-95% was achieved with both thermophilic and mesophilic MABRs and SBRs. The COD removal efficiency of thermophilic MABR (80-90%) was slightly lower than that of the mesophilic MABR (85-95%) and the thermophilic SBR (90-95%). A significant amount (13-37%) of COD was stripped by conventional aeration in the SBRs, while stripping in MABRs was negligible. Simultaneous COD removal and denitrification were observed in the mesophilic MABR, while the thermophilic MABR contributed mainly for COD removal. Nitrification was not significant in both the thermophilic and mesophilic MABRs. The results suggest that treatment of kraft evaporator condensate is feasible with the use of both thermophilic and mesophilic MABRs in terms of COD removal with the advantages of negligible stripping.


[Result of Z-palatoplasty for treating severe obstructive sleep apnea hypopnea syndrome].
To investigate the efficacy and related factors of Z-palatoplasty for treating severe obstructive sleep apnea hypopnea syndrome (OSAHS). Thirty-two severe OSAHS patients with Friedman II and III oropharyngeal airway had Z-palatoplasty. Twenty-three patients with modified Mallampti Index (MMI) III-IV had coblation tongue channeling (CTC) simultaneously. The patients were followed up for one year post operatively. After operation, the apnea and hypopnea index (AHI) decreased from (54.74 +/- 20.38)/h to (22.72 +/- 18.36)/h; the lowest artery oxygen saturation (LSaO2 ) increased from (0.74 +/- 0.08) to (0.85 +/- 0.14); the Epworth sleep scale (ESS) decreased from (12.24 +/- 5.78) to (5.35 +/- 3.62); the percentage of time with oxyhemoglobin saturation below 0.90 (CT90) decreased from (31.48 +/- 20.15) to (15.73 +/- 12.29). All of the differences were statistically significant (P < 0.01). According to related criterion of chinese journal of otorhinolaryngology head and neck surgery in 2009, accumulative excellence rate was 71.9% and accumulative valid rate 84.4%. Six patients had temporary velopharyngeal insufficiency and returned to normal after 3 months. Z-palatoplasty is an effective and safe surgical approach for OSAHS patients with Friedman II/III.


Origins of the "Third psychiatric revolution": the Community Mental Health Centers Act of 1963.
In recent decades the community mental health movement has achieved a dramatic reduction in the census of state and county mental hospitals in the United States, and hundreds of federally-funded community mental health centers have been established nationwide. At the same time, national controversy has arisen in response to what in places has seemed the haphazard process of implementing "deinstitutionalization" and the fate of many chronically mentally ill persons who are without needed social services and psychological care. Despite the widespread attention that this contemporary program has received, theoretical analysis of the complex social, scientific, intellectual, and political origins of America's community mental health policy remains deficient. This article examines the background and development of the Community Mental Health Centers Act of 1963, tracing how an important shift in national policy toward the mentally ill grew out of changing perceptions--among policymakers, professional groups, and the general citizenry in the post-World War II era--of the nature of the problem of mental illness.


Oocytes isolated from dairy cows with reduced ovarian reserve have a high frequency of aneuploidy and alterations in the localization of progesterone receptor membrane component 1 and aurora kinase B.
Oocytes isolated from cows of reproductive age with reduced antral follicle counts (AFC) have a diminished capacity of embryonic development, which may be related to alterations in the mechanism that directs the proper segregation of chromosomes. Because we demonstrated that progesterone receptor membrane component 1 (PGRMC1) is involved in chromosome congression and metaphase II (MII) plate formation, the present study was designed to determine 1) if the decrease in oocyte developmental competence observed in dairy cows with a reduced AFC is due to a higher incidence of aneuploidy and 2) whether alterations in PGRMC1 contributes to the incidence of aneuploidy. Oocytes from ovaries with reduced AFC and age-matched controls were matured in vitro and the occurrence of aneuploidy determined as well as the mRNA level and localization of PGRMC1. Although oocytes from ovaries with reduced AFC were capable of undergoing meiosis in vitro, these oocytes showed a 3-fold increase in aneuploidy compared to oocytes isolated from control ovaries (P < 0.05). Although Pgrmc1 mRNA levels were not altered, PGRMC1 and aurora kinase B (AURKB) failed to localize to precise focal points on MII chromosomes of oocytes from ovaries with reduced AFC. Furthermore, when oocytes of control ovaries were cultured with an inhibitor of AURKB activity, their MII plate was disrupted and PGRMC1 was not properly localized to the chromosomes. These results suggest that alterations in PGRMC1 and/or AURKB localization account in part for the increased aneuploidy and low development competence of oocytes from ovaries with reduced AFC.


Reduction of brain injury in neonatal hypoxic-ischemic rats by intracerebroventricular injection of neural stem/progenitor cells together with chondroitinase ABC.
Perinatal hypoxia-ischemia (HI) remains a critical issue. Cell transplantation therapy could be a potent treatment for many neurodegenerative diseases, but limited works on this kind of therapy have been reported for perinatal HI. In this study, the therapeutic effect of transplantation with neural stem/ progenitor cells (NSPCs) and chondrotinase ABC (ChABC) in a neonatal HI rat model is evaluated. Histological studies showed that the unaffected area of the brain in animals treated with NSPCs together with ChABC was significantly larger than that in the animals treated with vehicle or NSPCs alone. The wet weight of the brain that received the combined treatment was also significantly higher than those of the vehicle and their individual treatments. These results indicate that intracerebroventricular injection of NSPCs with ChABC reduces brain injury in a rat neonatal HI model.


Re-186(Sn) HEDP for treatment of painful osseous metastases: initial clinical experience in 20 patients with hormone-resistant prostate cancer.
Rhenium-186(tin) hydroxyethylidene diphosphonate (HEDP) is a new radiopharmaceutical that localizes in areas of osseous metastases in a manner similar to that of standard bone-scanning agents. It also emits beta particles with sufficient energy to be therapeutically useful. A single intravenous injection of about 33 mCi (1,221 MBq) was given to each of 20 elderly patients with advanced skeletal metastases from hormonally resistant prostate cancer. Prompt, significant relief of pain occurred 80% of the time with no significant side effects and only minimal, transient marrow toxicity. Re-186(Sn) HEDP appears to be a useful new agent for the palliation of painful osseous metastases in prostate cancer.


Intramyocardial Stem Cell Transplantation during Coronary Artery Bypass Surgery Safely Improves Cardiac Function: Meta-Analysis of 20 Randomized Clinical Trials.
IMSC transplantation during CABG is considered one of the most promising methods to effectively deliver stem cells and has been widely studied in many trials. But the results of outcomes and safety of this modality still vary widely. We conducted this meta-analysis of randomized controlled trials (RCTs) to evaluate not only the outcome but also the safety of this promising method. A meta-analysis was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. A comprehensive literature search was undertaken using the PubMed, Scopus, and Cochrane databases. Articles were thoroughly evaluated and analyzed. Twenty publications about IMSC during CABG were included. Primary outcomes were measured using LVEF, LVESV, LVESVI, LVESD, LVEDV, LVEDVI, LVEDD, WMSI, and 6-MWT. Safety measures were depicted by total deaths, MACE, CRD, CVA, myocardial infarction, ventricular arrhythmia, and cardiac-related readmission. IMSC transplantation during CABG significantly improved LVEF (MD = 3.89%; 95% CI = 1.31% to 6.46%; p = 0.003) and WMSI (MD = 0.28; 95% CI = 0.01-0.56; p = 0.04). Most of the other outcomes showed favorable results for the IMSC group but were not statistically significant. The safety analysis also showed no significant risk difference for IMSC transplantation compared to CABG alone. IMSC during CABG can safely improve cardiac function and tend to improve cardiac volumes and dimensions. The analysis and application of influencing factors that increase patients' responses to IMSC transplantation are important to achieve long-term improvement.


Pharmacokinetic interaction study between eslicarbazepine acetate and topiramate in healthy subjects.
Combination therapy is frequently required in the management of epilepsy. The primary objective of this study was to investigate the pharmacokinetic interaction between eslicarbazepine acetate (ESL) 1200 mg once daily and topiramate (TPM) 200 mg once daily in healthy subjects. Multiple-dose, open-label, one-sequence study in two parallel groups of 16 healthy male volunteers. After an 8-day treatment with ESL (Group A) or TPM (Group B), ESL and TPM were co-administered for 19 days. A bioequivalence approach based on a within-subject comparison was used to investigate a potential drug-drug interaction. End/start of treatment geometric mean ratios (GMR, %) and 90% confidence intervals (90% CI) were calculated for maximum plasma concentration (C(max)) and area under the plasma concentration-time curve over the dosing interval at steady-state (AUC(ss)) of eslicarbazepine (ESL major active metabolite), R-licarbazepine (ESL minor active metabolite) and TPM at Day 8 and Day 27. In Group A, eslicarbazepine GMR (90% CI) was 86.79% (81.06%; 92.94%) for C(max) and 92.70% (89.21%; 96.32%) for AUC(ss). In Group B, TPM GMR (90% CI) was 81.50% (77.48%; 85.89%) for C(max) and 81.81% (79.69%; 84.00%) for AUC(ss). The 90% CI of eslicarbazepine C(max) and AUC(ss) fell within the pre-specified bioequivalence range (80.00%; 125.00%), allowing it to be concluded that the extent of systemic exposure to eslicarbazepine was unaffected by the concomitant administration of TPM. The 90% CI for topiramate AUC(ss) was borderline in relation to the pre-specified bioequivalence range and topiramate C(max) fell outside the pre-specified bioequivalence range. Therefore, the extent of systemic exposure to TPM following co-administration with ESL was not formally bioequivalent to the extent of systemic exposure to TPM when TPM was administered alone. However, there was no difference between TPM elimination half-life following TPM co-administered with ESL and TPM administered alone (24.0 and 24.3 h, respectively). The bioavailability of R-licarbazepine was essentially bioequivalent. Two subjects discontinued due to adverse events. No clinical interaction appeared to be present in terms of adverse events when both drugs were given concomitantly. Concomitant administration of eslicarbazepine acetate 1200 mg once daily and topiramate 200 mg once daily showed no significant change in exposure to eslicarbazepine but an 18% decrease in exposure to topiramate, most likely caused by a reduced bioavailability of topiramate. No dose adjustment is required.


[Protein efficiency ratio of genetically modified corn with Cry1Ab-ma gene].
To evaluate the protein efficiency ratio(PER) of genetically modified corn with Cry1Ab-Ma gene and parental corn. Sixty SD rats(60-80 g) were randomly divided into genetically modified corn group, parental corn group and casein control group, with 20 rats in each group and half male and half female. Casein was added to 10% of the diet in casein control group. When the protein content of the diets in the genetically modified corn group and parental corn group was still less than 10% according to the principle of maximum incorporation, the defective part was supplemented with casein. Rats were free to drink and eat for 28 days. Food intake and body weight of each group were recorded every week. Blood was collected at the end of the experiment to determine hematology and blood biochemical indexes. The main organs were weighed and organ/body weigh indexes were calculated. PER and corrected PER were calculated. The body weight of all the animals in each group showed an increasing trend, and the weight growth was normal. Although there were statistical differences in the individual indexes of end-stage hematology and blood biochemical indexes, there was no biological significance. There were no significant change in the organ/body weigh indexes. PER of genetically modified corn, parental corn and casein were 2.01±0.22, 1.77±0.30 and 3.64±0.48, respectively. The corrected PER of genetically modified corn and parent corn were 1.38 and 1.22, respectively. The PER of this batch of genetically modified corn with Cry1Ab-ma gene was better than that of parental corn, but worse than that of casein.


Anatomic landmarks and time management during retroperitoneoscopic radical nephrectomy.
Retroperitoneoscopy has not been widely considered the preferred approach to laparoscopic radical nephrectomy for cancer, in part because the retroperitoneal anatomic landmarks have not been well defined. The aim of this study is to provide prospective, objective data on retroperitoneoscopic radical nephrectomy with regard to anatomic landmarks and time management of the sequential operative steps. A uniform database was devised to record predetermined intraoperative parameters prospectively in 18 consecutive retroperitoneoscopic radical nephrectomies. A three- or four-port technique was employed to perform 10 left and 8 right retroperitoneoscopic radical nephrectomies. Initial balloon dilation was routinely performed outside of and posterior to Gerota's fascia. The anatomic landmarks visible immediately on initial insertion of the laparoscope were: psoas muscle in 18 cases (100%), Gerota's fascia in 18 (100%), peritoneal reflection in 15 (83%), ureter and/or gonadal vein in 11 (61%), and renal artery pulsations in 10 (56%). Aortic pulsations were seen in 9 of 10 left (90%) and the inferior vena cava in 2 of 8 right (25%) radical nephrectomies. The mean surgical time was 203 +/- 52.9 minutes (range 105-290 minutes). The sequential operative steps and their individual time breakdowns were: port placement 12 +/- 3.9 minutes, hilar dissection 63 +/- 29.1 minutes, adrenal mobilization 49 +/- 12.1 minutes, specimen mobilization 19 +/- 20.8 minutes, and specimen entrapment and exit 23 +/- 18.2 minutes. When the initial balloon dilation resulted in visibility of four or more anatomic landmarks, the hilar dissection time was significantly shorter (P < 0.001). Proper development of the retroperitoneal space and identification of adequate anatomic landmarks is important during retroperitoneoscopy. This timed analysis of the sequential operative steps of retroperitoneoscopic radical nephrectomy has served as an important self-assessment tool for us in improving our surgical technique. As a result, our surgical time for retroperitoneoscopic radical nephrectomy has decreased from the earlier 4- to 5-hour range to the current 2- to 3-hour range.


[Different living environments as a factor differentiating cognitive function and activities of daily living in patients over 50 years of age ].
The aim of the dissertation was to com- pare the psychophysical state of people over 50 years of age from different societies. The first group consisted of 30 care home residents, the second group consisted of 30 participants of Active Senior Fair. In the research, two scales were applied: Mini-Mental State Examination, measuring the mental state, and Instrumental Activity of Daily Living, measuring agility in the field of complex everyday tasks. CONCLUSIONA: The study indicates the difference in the psychophysical state of both researched groups. The results may be connected with both age difference between groups and different living environment.


[Evaluation trial on the efficacy of neuroleptics on the outcome of schizophrenia].
Feasible and ideal methodological conditions lacking, we have tried an evaluation concerning the efficacy of neuroleptics upon the course of schizophrenia by comparing the evolution of homogeneous studies before and since the neuroleptic period. On the short term, neuroleptics are significantly more effective than the placebo upon schizophrenic symptoms and prevent the relapses in an noteworthy manner. On the long term, the evolution is significantly better for follow-up studies treated by neuroleptics (60% of patients improved) than for the non-treated follow-up studies i.e. before neuroleptic period (27.5% of patients improved). The time of the follow-up has an effect on the course of schizophrenia. Before neuroleptic periods, the schizophrenic process beyond 6 to 10 years was either stabilized or worsened. On the contrary, since the neuroleptic period, the number of improvements continued to increase after 12 years time (79.5% of patients improved for the follow-up beyond 12 years time versus 60% under 12 years). These improvements include paranoid and hebephrenic forms. On the contrary, catatonic forms had decreased very much since the utilization of neuroleptics (they moved from 18 to 28% before neuroleptic periods to 2% after the beginning of utilization of neuroleptics). If neuroleptics have undeniable action upon the schizophrenic symptomatology, they also act, on the long term, upon the social course of schizophrenia (30% of social remission before neuroleptic period versus 50% since neuroleptic period).


Results of controlled double-blind study of thyroid replacement in very low-birth-weight premature infants with hypothyroxinemia.
The nature of hypothyroxinemia in sick very low-birth-weight (VLBW) infants was evaluated by assessment of the hypothalamic-pituitary axis and by the clinical response to thyroxine (T4) therapy. Twenty-three very low-birth-weight infants of gestational age 26 to 28 weeks, whose serum T4 concentrations were 4 micrograms/dL on two occasions, and thyrotropin less than 20 microU/mL, were included in a double-blind study. Following a thyrotropin-releasing hormone stimulation test, babies were given either T4 or placebo. Nine babies were thyrotropin-releasing hormone tested prior to therapy; four babies, two from each group, were tested 1 to 2 weeks after therapy. In 11 untreated babies, mean base line serum thyrotropin of 7.0 +/- 1.4 rose to 23.7 +/- 4.1 microU/mL in 30 minutes. This response was not significantly greater than the observed response in full-term babies, 23.7 +/- 4.1 v 16.6 +/- 0.97 microU/mL, respectively, P greater than .05. In two babies treated with T4 the thyrotropin response to thyrotropin-releasing hormone was completely suppressed. Serial serum T4 determinations showed normalization in both groups after a similar time interval. There was no beneficial effect of T4 therapy on growth of head circumference, length, or weight. Developmental data revealed no significant differences in the mental, motor, or gross neurologic outcome in the treated and nontreated infants after 1 year of follow-up. These observations imply that hypothyroxinemia in sick preterm infants is not a direct consequence of hypothyroidism. Despite the lack of demonstrable short-term beneficial effects of T4 therapy, follow-up studies are necessary to resolve the question of long-term benefits.


An oxidative DNA "damage" and repair mechanism localized in the VEGF promoter is important for hypoxia-induced VEGF mRNA expression.
In hypoxia, mitochondria-generated reactive oxygen species not only stimulate accumulation of the transcriptional regulator of hypoxic gene expression, hypoxia inducible factor-1 (Hif-1), but also cause oxidative base modifications in hypoxic response elements (HREs) of hypoxia-inducible genes. When the hypoxia-induced base modifications are suppressed, Hif-1 fails to associate with the HRE of the VEGF promoter, and VEGF mRNA accumulation is blunted. The mechanism linking base modifications to transcription is unknown. Here we determined whether recruitment of base excision DNA repair (BER) enzymes in response to hypoxia-induced promoter modifications was required for transcription complex assembly and VEGF mRNA expression. Using chromatin immunoprecipitation analyses in pulmonary artery endothelial cells, we found that hypoxia-mediated formation of the base oxidation product 8-oxoguanine (8-oxoG) in VEGF HREs was temporally associated with binding of Hif-1α and the BER enzymes 8-oxoguanine glycosylase 1 (Ogg1) and redox effector factor-1 (Ref-1)/apurinic/apyrimidinic endonuclease 1 (Ape1) and introduction of DNA strand breaks. Hif-1α colocalized with HRE sequences harboring Ref-1/Ape1, but not Ogg1. Inhibition of BER by small interfering RNA-mediated reduction in Ogg1 augmented hypoxia-induced 8-oxoG accumulation and attenuated Hif-1α and Ref-1/Ape1 binding to VEGF HRE sequences and blunted VEGF mRNA expression. Chromatin immunoprecipitation-sequence analysis of 8-oxoG distribution in hypoxic pulmonary artery endothelial cells showed that most of the oxidized base was localized to promoters with virtually no overlap between normoxic and hypoxic data sets. Transcription of genes whose promoters lost 8-oxoG during hypoxia was reduced, while those gaining 8-oxoG was elevated. Collectively, these findings suggest that the BER pathway links hypoxia-induced introduction of oxidative DNA modifications in promoters of hypoxia-inducible genes to transcriptional activation.


Evolutionary Loss of the Ability of the Photosystem I Primary Electron Donor for the Redox Interaction with Mn-Bicarbonate Complexes.
The structure and functional organization of the photosystem I (PSI) reaction center (RC) donor side has a significant similarity to the reaction centers of purple bacteria (bRCs), despite the fact that they belong to different types of RCs. Moreover, the redox potential values of their primary electron donors are identical (~0.5 V). In our earlier reports [Khorobrykh et al. (2008) Phylos. Trans. R. Soc. B., 363, 1245-1251; Terentyev et al. (2011) Biochemistry (Moscow), 76, 1360-1366; Khorobrykh et al. (2018) ChemBioChem, 14, 1725-1731], we have demonstrated redox interaction of low-potential Mn2+-bicarbonate complexes with bRCs, which might have been one of the first steps in the evolutionary origin of Mn-cluster of the photosystem II water-oxidizing complex that occurred in the Archean (over 3 billion years ago). In this study, we investigated redox interactions between Mn2+-bicarbonate complexes and PSI. Such interactions were almost absent in the original PSI preparations and emerged only in preoxidized PSI preparations containing ~50% oxidized RCs. The interaction between Mn2+-bicarbonate complexes and PSI required increased Mn2+ concentrations, while its dependence on the HCO3- concentration indicated involvement of electroneutral low-potential [Mn(HCO3)2] complex in the process. Analysis of the PSI crystal structure revealed steric hindrances on the RC donor side, which could block the redox interaction between Mn2+-bicarbonate complexes and oxidized primary electron donor. Comparison of structures of RCs from the PSI and ancient RCs from heliobacteria belonging to the same type of RCs suggested that such hindrances should be absent in the primitive PSI in the Archean and allowed to explain their evolutionary origin as a consequence of PSI RCs into the united electron transport chain (ETC) of the photosynthetic membrane that was accompanied by the evolutionary loss of PSI capacity for the redox interaction with Mn2+-bicarbonate complexes.


Do formulation differences between the reference listed drug and generic piperacillin-tazobactam impact reconstitution?
Pharmaceutical differences between the reference listed drug (RLD) and generic formulations of piperacillin-tazobactam may impact the reconstitution process for intravenous administration. This study evaluated the RLD against three generic formulations and measured their reconstitution times using a standardized process. The mean (standard deviation [SD]) reconstitution time for one generic formulation was 5.57 (1.49) min, which was 35% to 42% longer (P < 0.002) than that for the RLD and two other formulations. Observable microscopic differences in powder particle morphology may explain these findings.


Headache in systemic lupus erythematosus: a controlled study.
Intractable headaches, the so-called 'lupus headaches', have been long thought of as a common and characteristic manifestation of systemic lupus erythematosus (SLE). Seventy-eight patients with SLE, including 10 patients with definite central nervous system (CNS) involvement, and 89 healthy individuals matched for age, sex and socioeconomic status, were studied by a specific questionnaire addressing the characteristics and type of headache. Clinical features of SLE, neurological manifestations and treatment, disease severity and autoantibody profiles were correlated to the presence of headache. One year prevalence of headache was similar between patients (32%) and otherwise healthy individuals (30%). No significant differences regarding frequency, family history of headache and need for analgesic medication were observed. Headache refractory to analgesic treatment, but responsive to corticosteroid regimen, was recorded in only one patient. Clinical and serological features of SLE, including Raynaud's phenomenon and the presence of anticardiolipin antibodies, were not significantly different between headache sufferers and non-sufferers. In the majority of patients reporting headache, anxiety and/or depression co-existed. Episodic tension headache was the most frequent type, while migraine was traced in a quarter of headache sufferers. Neither the presence nor the clinical type of headache was related to, or predictive of, the development of seizures or psychosis. These results indicate that headache is not specifically related to SLE expression or severity, and suggest that accepting the presence even of a severe headache as a neurological manifestation of SLE in the absence of seizures or overt psychosis may result in overestimation of the disease status.


Progesterone and calcitriol reduce invasive potential of endometrial cancer cells by targeting ARF6, NEDD9 and MT1-MMP.
Previously, we have demonstrated that progesterone and calcitriol synergistically inhibit growth of endometrial and ovarian cancer by enhancing apoptosis and causing cell cycle arrest. Metastasis is the main reason of mortality in cancer patients. Activation of ADP-Ribosylation Factor 6 (ARF6), Neural Precursor cell expressed Developmentally Downregulated 9 (NEDD9), and Membrane-Type-1 Matrix Metalloproteinase (MT1-MMP) have been implicated in promoting tumor growth and metastasis. We examined the effects of progesterone, calcitriol and progesterone-calcitriol combination on metastasis promoting proteins in endometrial cancer. Expression of ARF6, NEDD9, and MT1-MMP was enhanced in advanced-stage endometrial tumors and in cancer cell lines compared to normal tissues and immortalized EM-E6/E7-TERT endometrial epithelial cells. Knockdown of these proteins significantly inhibited the invasiveness of the cancer cells. The expression levels of all three proteins was reduced with progesterone and progesterone-calcitriol combination treatment, whereas calcitriol alone showed no effect on their expression but moderately decreased MT1-MMP activity. Fluorescence microscopy showed membrane expression of MT1-MMP in vehicle and calcitriol-treated endometrial cancer cells. However, progesterone and calcitriol-progesterone combination treatment revealed MT1-MMP in the cytoplasm. Furthermore, progesterone and calcitriol reduced the activity of MT1-MMP, MMP-9, and MMP-2. In addition, invadopodia regulatory proteins were attenuated in both progesterone and progesterone-calcitriol combination treated cells as well as in MT1-MMP knockdown cells. Thus, targeting the aberrant MT1-MMP signaling with progesterone-calcitriol may be a novel approach to impede MT1-MMP mediated cancer dissemination and may have therapeutic benefits for endometrial cancer patients.


Effects of oral supplementation with bovine colostrum on the immune system of weaned piglets.
The aim of this study was to evaluate the influence of bovine colostrum supplementation on the immune system of weaned piglets in a context of a full ban of in-feed antibiotics. After weaning at 21 days, 24 outbred piglets were fed with a diet supplemented daily for three weeks with 0, 1 or 5 g of colostrum. Feed intake, growth performance, haematological parameters, and serum and local anti-colostrum immunoglobulin levels were examined. Lymphocytes from the blood, spleen, and gut-associated lymphoid were analysed for phenotype as well as for their ability to produce cytokines. The stimulation index (SI) of mononuclear cells from different organs was obtained after colostral or mitogenic stimulation. Feed intake, growth, and haematological parameters were not significantly affected by colostrum. Total serum IgA levels were increased after colostrum supplementation, with a transient decrease in total IgG. Local anti-colostrum immunization was observed in colostrum-fed piglets. The CD21+/CD3+ cells populations of the ileal Peyer's patch (iPP) were markedly affected. The SI of lymphocyte populations changed significantly whereas, naive blood lymphocytes were not stimulated in vitro in the presence of bovine colostrum, suggesting local anti-colostrum immunization and an absence of direct mitogenic effects of the colostrum. Both Th1 and Th2 cytokine production was present in the different organs of colostrum-fed piglets. Bovine colostrum especially stimulated iPP cells.


Short-term impact of the COVID-19 pandemic on patients with a chronic pain disorder.
The current Covid-19 pandemic has already had a definite impact on the daily life of many people worldwide. It has been proposed that people with preexisting medical conditions will be harder hit by the pandemic and the subsequent measures to contain the spread of the disease. In this questionnaire-based, observational study, we aimed to assess the impact of the pandemic on patients with a chronic pain disorder, who are treated at a tertiary multidisciplinary pain center.Participants rated the impact of the pandemic on their chronic pain disorder using a self-designed questionnaire. Also, participants filled out the regular follow-up questionnaire to assess a chronic pain disorder measuring among other parameters pain intensity, symptoms of depression, anxiety, stress, and pain-related quality of life.Of 136 eligible patients who presented to our pain center between May 5th and July 17th, 112 agreed to participate in the study (82.4%). Eighty two participants (73.2%) reported a deterioration of the pain disorder using the self-designed questionnaire. The more robust parameters of the regular follow-up questionnaire showed no relevant changes compared to data collected before the pandemic. We were not able to detect any demographic and medical parameters that were clinically relevantly associated with a higher impact of the pandemic.We conclude that a chronic pain disorder is a relatively stable disease that does not change significantly due to external factors, like the Covid-19 pandemic, even if the subjective impact is perceived to be high.


Detecting Genotype-Population Interaction Effects by Ancestry Principal Components.
Heterogeneity in the phenotypic mean and variance across populations is often observed for complex traits. One way to understand heterogeneous phenotypes lies in uncovering heterogeneity in genetic effects. Previous studies on genetic heterogeneity across populations were typically based on discrete groups in populations stratified by different countries or cohorts, which ignored the difference of population characteristics for the individuals within each group and resulted in loss of information. Here, we introduce a novel concept of genotype-by-population (G × P) interaction where population is defined by the first and second ancestry principal components (PCs), which are less likely to be confounded with country/cohort-specific factors. We applied a reaction norm model fitting each of 70 complex traits with significant SNP-heritability and the PCs as covariates to examine G × P interactions across diverse populations including white British and other white Europeans from the UK Biobank (N = 22,229). Our results demonstrated a significant population genetic heterogeneity for behavioral traits such as age at first sexual intercourse and academic qualification. Our approach may shed light on the latent genetic architecture of complex traits that underlies the modulation of genetic effects across different populations.


Laser Doppler vibrometry measurement of the mechanical myogram.
Contracting muscles show complex dimensional changes that include lateral expansion. Because this expansion process is intrinsically vibrational, driven by repetitive actions of multiple motor units, it can be sensed and quantified using the method of Laser Doppler Vibrometry (LDV). LDV has a number of advantages over more traditional mechanical methods based on microphones and accelerometers. The LDV mechanical myogram from a small hand muscle (the first dorsal interosseous) was studied under conditions of elastic loading applied to the tip of the abducted index finger. The LDV signal was shown to be related systematically to the level of force production, and to compare favorably with conventional methods for sensing the mechanical and electrical aspects of muscle contraction.


Growing a classification tree using the apparent misclassification rate.
A method to determine the size of a classification tree is proposed. This method is based on the change of the apparent misclassification rate (AMR) of the tree at each growing stage. The method is simple and fast compared to the other classification tree methods, which are based on minimizing a cost complexity function. To test the method, it was used to classify species of fungi, and the results are in good agreement with those obtained by linear discriminant analysis. Also, 21 proteins with known structures and functions were classified using the proposed method. For this purpose the coefficient of variation for several properties of the secondary structures of these proteins has been used. Again, the results were in good agreement with the classification obtained previously using dynamic programming.


Comparison of phasing methods for sulfur-SAD using in-house chromium radiation: case studies for standard proteins and a 69 kDa protein.
Phasing of the crystal structures of four standard proteins (lysozyme, trypsin, glucose isomerase and thaumatin) and a novel 69 kDa protein from Thermus thermophilus, TT0570, was performed using the single-wavelength anomalous diffraction of S atoms intrinsically present within the native protein molecules. To utilize the sulfur anomalous diffraction, the data sets were collected using the loopless data-collection method with chromium Kalpha X-rays of wavelength 2.29 A. Three phasing methods, MLPHARE, SHARP and OASIS-2004, were tested in combination with the DM or SOLOMON density-modification method. The results showed that the solvent contents are still an important factor for phasing with the S-SAD method, even when longer wavelength Cr Kalpha radiation is used. Of the three procedures, the improved direct phasing of OASIS-2004 with its implemented fragment feedback to the direct-method probability calculation gave the best results in determining the initial phases. For all five proteins, almost the entire models could be built automatically.


Natural History of Anemia and Efficacy and Safety of Oral Iron Therapy in Children Newly Diagnosed With Inflammatory Bowel Disease.
Anemia is one of the most common extraintestinal manifestations of pediatric inflammatory bowel disease (IBD). We aimed to evaluate the prevalence of anemia in children newly diagnosed with IBD and assess the efficacy and safety of oral iron therapy over a 12-month follow-up period. This single-center, retrospective, observational cohort study included all children newly diagnosed with IBD at the Pediatric Gastroenterology Unit of Sapienza University of Rome from May 2015 to May 2019 presenting with anemia. At baseline, demographic, clinical, laboratory data (hemoglobin, mean corpuscular volume, serum iron, ferritin, transferrin levels, erythrocyte sedimentation rate, and C-reactive protein), and treatment received, were recorded. Clinical and laboratory data, as well as anemia therapy and adverse events (AEs), were collected every 3 months during the 1-year follow-up. Eighty-nine out of 140 patients newly diagnosed with IBD presented with anemia (64%); 13 were excluded due to incomplete follow-up, thus 76 were included [median age 12.7 (interquartile range 9.8-15), 25 (33%) Crohn disease, 51 (67%) ulcerative colitis]. All patients received sucrosomial iron (SI) alone or in combination with intravenous ferric carboxymaltose. Treatment with SI was effective in 67 (88%) patients at the end of follow-up [37 (48%) within 3 months], regardless of anemia severity at baseline. No serious AEs related to SI treatment were reported. We confirmed a high prevalence of anemia at the time of the diagnosis of pediatric IBD. Our data suggest that SI is safe and effective, leading to anemia resolution in approximately half of the patients within 3 months.


Temporal variations in the infection of a population of Clypeomorus bifasciata (Gastropoda: Prosobranchia) by a digenean microphallid larva in Kuwait Bay.
The prosobranch snail Clypeomorus bifasciata in Kuwait Bay was examined for digenean infections over a one year period during 1994/1995. A total of 1500 snails was examined and 567 (37.8%) were found to harbour nine digenean species. The prevalence of a microphallid species was 33.9% while each of the others occurred in less than 1.2% of the snails. The prevalence of infection increased with shell size. Multiple infections were observed in only five of the infected snails and the microphallid was involved in all of them. Snails were infected with the microphallid throughout the year and there appeared to be two peaks in the proportion of infected snails shedding cercariae, a winter peak from November to January and a summer peak from June to August. The crab Xantho exaratus collected from snail sampling sites was heavily parasitized by microphallid metacercariae of the genera Longiductotrema and Microphallus. This is the first report on microphallid metacercariae in crabs in the Arabian Gulf region.


Molecular genetic study of introgression between Saccharomyces bayanus and S. cerevisiae.
The genomic constitution of different S. bayanus strains and natural interspecific Saccharomyces hybrids has been studied by genetic and molecular methods. Unlike S. bayanus var. uvarum, some S. bayanus var. bayanus strains (the type culture CBS 380, CBS 378, CBS 425, CBS 1548) harbour a number of S. cerevisiae subtelomeric sequences: Y', pEL50, SUC, RTM and MAL. The two varieties, having 86-100% nDNA-nDNA reassociation, are partly genetically isolated from one another but completely isolated from S. cerevisiae. Genetic and molecular data support the maintaining of var. bayanus and var. uvarum strains in the species S. bayanus. Using Southern hybridization with species-specific molecular markers, RFLP of the MET2 gene and flow cytometry analysis, we showed that the non-S. cerevisiae parents are different in lager brewing yeasts and in wine hybrid strains. Our results suggest that S. pastorianus is a hybrid between S. cerevisiae and S. bayanus var. bayanus, while S. bayanus var. uvarum contributed to the formation of the wine hybrids S6U and CID1. According to the partial sequence of ACT1 gene and flow cytometry analysis, strain CID1 is a triple hybrid between S. cerevisiae, S. kudriavzevii and S. bayanus var. uvarum.


Bibliometric Assessment of the Global Scientific Production of Nitazoxanide.
Nitazoxanide is a member of a new class of drug, thiazolides, and it was discovered in 1984 with antimicrobial activity effect against anaerobic bacteria, Hepatitis virus, protozoa, and helminths. A bibliometric study on four databases (1984-2016) - Medline, Scopus, LILACS, and SciELO - characterizing the global scientific production of nitazoxanide. We determined the quantity, quality (number of citations), and types of studies developed by each country, characterizing them by years, international cooperation, development, place of publication, authors (with its H-index), and groups with higher impact. There were 512 articles in Medline - the higher scientific production is from the USA (19.71%), Switzerland (7.51%), and Mexico (7.27%). There were 1,440 articles in Scopus - from the USA (8.98%), Mexico (2.13%), and India (1.65%). There were 405 articles in LILACS - from Mexico (4.69%), the USA (4.2%), and Peru (2.47%). There were 47 articles in SciELO - from Brazil (34.04%), Venezuela (21.28%), and Colombia (14.89%). The H-index of nitazoxanide is 75 - the USA (26), Egypt (12), and Canada (10) were the countries contributing more with that. Nitazoxanide research has been highly important. Nevertheless, it is relatively limited when compared with other drugs. Its research has been led by the USA, as revealed in this bibliometric assessment. Although some developing countries, where it is used especially for protozoa and helminths, probably have its influence, and this explains the fact that Mexico and India, among others, are the top countries in the scientific production of this anti-infective agent. This bibliometric study evidenced a relatively low number of publications, however, it has been increased in recent years.


Structure of bacterial L forms and their parent bacteria.
Weibull, Claes (Rocky Mountain Laboratory, Hamilton, Mont.). Structure of bacterial L forms and their parent bacteria. J. Bacteriol. 90:1467-1480. 1965.-Light and electron microscopic studies were done on normal cells and L forms of Proteus mirabilis, Staphylococcus aureus, and Corynebacterium sp. grown in liquid media. Under the prevailing growth conditions, the L forms studied were morphologically indistinguishable from one another. They appeared as approximately spherical elements occurring singly or more often connected with each other by thinner portions of cell material. In sections of large L forms, the following structures were seen: a peripheral, triple-layered ("unit") membrane, a granular cytoplasm, nuclear regions, and vacuoles limited by membranes. Small bodies often were present inside the vacuoles. These bodies also contained a peripheral membrane and a granular cytoplasm but usually no nuclear regions. The normal bacteria from which the L forms were derived differed markedly in structure from one another, especially in the surface layers of the cells.


Endocytosis in renal proximal tubules. Experimental electron microscopical studies of protein absorption and membrane traffic in isolated, in vitro perfused proximal tubules.
The present study provides at least partly answers to some of the questions outlined in the introduction (see also Figs. 2 and 3): Endocytosis and intracellular transport of ferritin, HRP and insulin tracers (125I-insulin, native insulin and insulin-gold) was followed by use of EM-autoradiography, immunocytochemistry and cytochemistry. Proteins are internalized into endocytic vacuoles and transferred to the lysosomes for degradation. Tracers were not transferred to the Golgi apparatus. 125I-insulin is internalized by specific receptor mediated endocytosis from the apical plasma membrane, substantiating the hypothesis that specific endocytosis receptors are responsible for reabsorption of certain proteins. The binding sites are localized in endocytic invaginations and in the microvillus membrane. The binding sites in the invaginations are responsible for endocytosis, whereas the function of the microvilli binding sites is unclear, but they possess the ability to migrate in the plane of the microvillus membrane. Binding to specific binding sites and subsequent internalization of insulin takes place with high efficiency corresponding to more than 50% of the perfused load. Not all proteins are reabsorbed with high efficiency e.g. EGF which has similar molecular weight and pI is shown to be reabsorbed with substantially lower efficiency (about 4%). Binding and absorption efficiency of insulin may also change due to alterations in flow rate and perfused loads of protein: The load determines the magnitude of uptake and the flow rate determines the efficiency in binding and uptake. These changes are suggested to be caused by concomitant changes in the mean luminal concentration. The reabsorption process for insulin is efficient and of large capacity, and is only saturable (Michaelis-Menten kinetics) at very high concentrations of insulin. The proximal tubular internalization and degradation of 125I-insulin reach steady state rapidly. The processing can be described by a two-compartment model with t1/2 for transfer of 125I-insulin to lysosomes of 8.5 min and for lysosomal degradation of 72 min. 125I-PYY a linear peptide with similar molecular weight as EGF and insulin is not endocytosed but extracted with high efficiency (75% removed) by degradation by brush border peptidases and a substantial transtubular transport of TCA-precipitable PYY takes place by a paracellular route. A small vesicular transport of colloidal tracers was demonstrated constituting about 0.5% of the endocytosed amount. A method for covalently cross-linking insulin tracers to apical binding sites is described and evaluated. Recycling of apical binding sites was estimated to be very efficient and did not involve lysosomes or the Golgi apparatus.(ABSTRACT TRUNCATED AT 400 WORDS)


Clinical Features and Resistance to Entecavir Monotherapy of Patients with Hepatitis B.
Hepatitis B virus (HBV) infection is a major public health concern worldwide. Entecavir (ETV), a first-line nucleos(t)ide analogue (NA) for HBV, has a low risk of resistance. We evaluated the efficacy of ETV monotherapy, ratio of ETV-resistant, and the clinical features of patients with ETV resistance. A total of 130 patients (72 males, 58 females; mean age, 61 ± 15 years) were divided into a NA-naïve group (n = 108) and NA-experienced group (n = 22). We examined the clinical outcomes of ETV monotherapy and associated factors. We also assessed the clinical features of 15 patients with resistance to ETV (mean, 51.0 ± 27.4 weeks). Among the 130 patients, 94.1% achieved ALT normalization and 63.6% achieved serum HBV DNA negativity after ETV monotherapy for 96 weeks. Of the patients in the NA-naïve group, 93.1% and 60.4% achieved ALT normalization and HBV DNA negativity, respectively. Of the patients in the NA-experienced group, 100% and 74.9% achieved ALT normalization and HBV DNA negativity, respectively. Compared to patients on ETV continuously, 15 ETV-resistant patients had a higher baseline HBV viral load. There was a significant difference in the time to HBV DNA negativity, but not ALT normalization after ETV monotherapy in these groups. Rescue treatment with other NAs led to ALT normalization in all of these patients, but not HBV DNA negativity. ETV monotherapy has a long-term clinical efficacy. While some patients especially with HBV DNA high viral load developed ETV resistance, rescue treatment led to ALT normalization in these patients.


Postoperative Epidural Hematomas in the Lumbar Spine.
Postoperative epidural hematomas are rare complications following lumbar spine surgery, but if they are not quickly identified and treated they can lead to permanent neurological deficits. Epidural hematomas occur in approximately 0.10%-0.24% of all spine surgeries, and despite the fact that multiple large studies have been performed attempting to identify risk factors for this complication, there is still significant debate about the effect of subfascial drains, postoperative anticoagulation, and antiplatelet medication on the incidence of postoperative hematoma. The purpose of this manuscript is to review the epidemiology, etiology, diagnosis, and treatment of patients who develop a postoperative lumbar epidural hematoma.


Effects of acute administration of the GABA(B) receptor agonist baclofen on behavioral flexibility in rats.
The ability to adjust response strategies when faced with changes in the environment is critical for normal adaptive behavior. Such behavioral flexibility is compromised by experimental disruption of cortical GABAergic signaling, as well as in conditions such as schizophrenia and normal aging that are characterized by cortical hyperexcitability. The current studies were designed to determine whether stimulation of GABAergic signaling using the GABA(B) receptor agonist baclofen can facilitate behavioral flexibility. Male Fischer 344 rats were trained in a set-shifting task in which they learned to discriminate between two response levers to obtain a food reward. Correct levers were signaled in accordance with two distinct response rules (rule 1: correct lever signaled by a cue light; rule 2: correct lever signaled by its left/right position). The order of rule presentation varied, but they were always presented sequentially, with the trials and errors to reach criterion performance on the second (set shift) rule providing the measure of behavioral flexibility. Experiments determined the effects of the GABA(B) receptor agonist baclofen (intraperitoneal, 0, 1.0, 2.5, and 4.0 mg/kg) administered acutely before the shift to the second rule. Baclofen enhanced set-shifting performance. Control experiments demonstrated that this enhancement was not simply due to improved discrimination learning, nor was it due to impaired recall of the initial discrimination rule. The results demonstrate that baclofen can facilitate behavioral flexibility, suggesting that GABA(B) receptor agonists may have utility for treating behavioral dysfunction in neuropsychiatric disorders.


Tissue donation: what does it mean to families?
Previous research has described families' responses and experiences with the donation process; however, little attention has been paid to families linked to tissue banks that have no affiliation with hospitals or organ procurement agencies. To assess the impact of approaches made to families who consented to tissue donation with the Donor Tissue Bank of Victoria, Australia, and to examine how this information could be used to improve the existing service. An evaluation questionnaire was developed and consisted of 15 questions. The questionnaire was part of a structured follow-up service and was given only to 339 families who consented to donation. Families who are approached about tissue donation are contacted within 24 hours of their family member's death. They are coping with the sudden unexpected death of a family member and have little knowledge of tissue donation or the donor tissue bank. Fifty-eight percent of participants completed the questionnaire. The data were quantitatively and qualitatively examined. The skills and procedures utilized by the transplant coordinators are affirmed by the results, and respondents appear to find contact with the donor tissue bank positive at a terrible time in their lives. Approaches to families must be made sensitively and sufficient information must be given to enable decision making.


Gradation of kainic acid-induced rat limbic seizures and expression of hippocampal heat shock protein-70.
Systemic injection of kainic acid (KA) induces limbic seizures in rats, which resemble human temporal lobe epilepsy, the most common form of adult human epilepsy. In this study, we have investigated KA-elicited limbic seizures in the rats by correlating the severity of the seizure attacks with the expression of hippocampal heat shock protein-70 (HSP70) which has been suggested to be a marker for neuronal injury/death in this model of seizures. After a systemic injection of KA, six stages of limbic seizures have been classified, namely, staring (stage 1), wet dog shake (stage 2), hyperactivity (stage 3), rearing (stage 4), rearing and falling (stage 5), and jumping (stage 6). Stages 4, 5 and 6 were further divided into mild and severe sub-stages. HSP70 expression was not detected in animals with stages 1 and 2 seizures. At stage 3 a small amount of HSP70 immunoreactive neurons was detected in the CA3 field and the dentate hilus. From stage 4 to stage 5 the degree of HSP70 immunoreactivity increased in the CA1 field from a few positive cells in stage 4 mild to large numbers of immunoreactive neurons in stage 5 severe. HSP70 became detectable in pyramidal cells in the CA2 field from stage 5 severe and higher. In animals with stage 6 seizures, the majority of HSP70 expression became located in glial cells throughout the whole hippocampus. We concluded that HSP70 expression in the hippocampus positively correlates with the severity of KA-elicited limbic seizures.